Long Noncoding RNA SNHG5 Induces the NF-κB Pathway by Regulating miR-181c-5p/CBX4 Axis to Promote the Progression of Non-Small Cell Lung Cancer

ObjectiveExplorations have been progressing in decoding the mechanism of non-small cell lung cancer (NSCLC). However, long noncoding RNA small nucleolar RNA host gene 5/microRNA-181c-5p/chromobox protein 4 (SNHG5/miR-181c-5p/CBX4) axis-oriented mechanisms in NSCLC is still in infancy. Therein, this study is proposed to probe this axis in NSCLC progression.MethodsSamples of 86 NSCLC patients were collected and SNHG5, miR-181c-5p and CBX4 expression was detected in NSCLC tissues and cells. NSCLC cells were transfected with plasmids to change SNHG5, miR-181c-5p or CBX4 expression, after which cell functions and phosphorylated (p)-nuclear factor (NF)-κB protein expression were evaluated. The relationships among SNHG5, miR-181c-5p and CBX4 were validated. Tumor xenografts were implemented to verify the roles of SNHG5, miR-181c-5p and CBX4 in tumor growth.ResultsLow miR-181c-5p and high SNHG5 and CBX4 levels were found in NSCLC tissues and cells. Restoration of miR-181c-5p or knockdown of SNHG5 or CBX4 restrained NSCLC cell progression and inactivated the NF-κB pathway. Upregulated CBX4 abolished the effects of miR-181c-5p on reducing NSCLC cell progression. SNHG5 regulated the interaction between miR-181c-5p and CBX4. In vivo, restoration of miR-181c-5p or knockdown of SNHG5 or CBX4 retarded the tumor growth.ConclusionThis study has delineated that SNHG5 induces the NF-κB pathway by regulating the miR-181c-5p/CBX4 axis to promote NSCLC progression, which may pave a novel path for NSCLC treatment.     

microRNA-100在急性髓细胞白血病中的预后评估价值研究

目的探讨骨髓细胞microRNA-100表达水平对急性髓细胞白血病（AML）患者的预后评估价值。方法选取核型正常AML（CN-AML）患者154例,采用荧光定量RT-PCR法检测骨髓细胞microRNA-100的表达水平,将数值大于等于中位数者归为高表达组,低于中位数者归为低表达组。比较microRNA-100高表达组与低表达组患者的临床特征,包括性别、年龄、FAB分型、Hb、WBC、PLT、原始细胞比例、FLT3-ITD基因突变、NPM1基因突变、化疗后完全缓解情况等。随访48个月,观察并比较两组患者总生存、无事件生存率。结果与高表达组患者比较,低表达组患者的FAB分型M4、M5型比例较高（P＜0.05）,Hb水平较低（P＜0.05）,原始细胞比例较低（P＜0.05）。两组患者性别、年龄、WBC、PLT、FLT3-ITD基因突变、NPM1基因突变、化疗后完全缓解情况比较均无统计学意义（均P＞0.05）。microRNA-100低表达组患者总生存率、无事件生存率均低于高表达组患者（均P＜0.05）。结论microR-NA-100低表达或是AML患者预后差的评估指标。     

Association between circulating microRNA-208a and severity of coronary heart disease

Circulating microRNA (miR)-208a is specifically expressed in the heart muscle, which is involved in the regulation of myosin during cardiac development. Previous studies reported that cardiac-specific miR-208a level is significantly higher in plasma of coronary heart disease (CHD) patients. However, whether it correlates with severity of CHD, has never been elucidated before. The aim of this study was to explore the association between miR-208a and the presence and severity of CHD. Samples were collected from 290 CHD patients and 110 subjects with angiographic exclusion of CHD. Circulating miRNA-208a expression was detected using quantitative real-time PCR. The Gensini score was used to evaluate the severity of coronary stenotic lesions. Expression of miRNA-208a was identified on the basis of the quartiles of the Gensini score, and association between the miRNA-208a levels and CHD was analyzed. Diagnostic potential of miR-208a of CHD was performed by ROC analysis. CHD patients had higher miRNA-208a expression (1.61, 0.45–3.86 vs. 0.66, 0.11–1.42, p?p?r?=?0.8525, p?p?相似文献   

老年慢性心力衰竭患者血清microRNA-208a、CASP3与心室重构和预后的关系

目的 探讨老年慢性心力衰竭(CHF)患者血清microRNA-208a(miR-208a)、含半胱氨酸的天冬氨酸蛋白水解酶3(CASP3)与心室重构和预后的关系。方法 选取2019年1月—2021年9月新余市中医院收治的155例老年CHF患者为CHF组,另选取同期该院体检健康者57例为对照组,CHF组患者根据预后情况分为预后不良组(58例)和预后良好组(97例)。实时荧光定量聚合酶链反应(qRT-PCR)检测miR-208a mRNA相对表达量;酶联免疫吸附试验(ELISA)检测CASP3、B型脑利钠肽(BNP)水平;采用Pearson/Spearman相关系数分析老年CHF患者血清miR-208a、CASP3与BNP、右心室内径(RVD)、左心室舒张末期内径(LVEDD)、左心室短轴缩短率(LVFS)、左室射血分数(LVEF)、左心室质量指数(LVMI)的相关性;多因素Logistic回归分析老年CHF患者预后不良的影响因素;绘制受试者工作特征(ROC)曲线分析血清miR-208a、CASP3对老年CHF患者预后不良的预测价值。结果 CHF组血清miR-208a、CASP3、BNP水...     

磁共振成像联合血清microRNA-221对前列腺癌的诊断价值

目的 探讨磁共振成像（MRI）结合血清microRNA-221-221（miR-221）检测在前列腺癌诊断中的价值。方法 回顾性分析2019年5月—2023年1月襄阳市中心医院收治的103例疑似前列腺癌患者的临床资料,将前列腺穿刺病理结果作为金标准。所有患者行磁共振弥散加权成像（MRI-DWI）、动态增强磁共振成像（MRI-DCE）及血清miR-221检测,分析MRI参数、miR-221诊断前列腺癌的价值。结果 穿刺活检病理诊断结果显示,103例前列腺癌疑似患者中,73例诊断为前列腺癌。前列腺癌患者表现弥散系数（ADC）值低于非前列腺癌患者（P <0.05）。前列腺癌患者容积转运常数（K_trans）高于非前列腺癌患者（P <0.05）,前列腺癌与非前列腺癌患者的速率常数（K_ep）、细胞外间隙对比剂容积分数（V_e）比较,差异均无统计学意义（P >0.05）。前列腺癌患者miR-221相对表达量高于非前列腺癌患者（P <0.05）。ROC曲线分析结果显示,ADC、K_trans、miR-221及3者联合诊断前列腺癌的敏感性分别为72.60%（95% CI：0.607,0.821）、69.86%（95% CI：0.578,0.798）、73.97%（95% CI：0.622,0.832）、82.19%（95% CI：0.711,0.898）,特异性分别为80.00%（95% CI：0.609,0.916）、73.33%（95% CI：0.538,0.870）、70.00%（95% CI：0.504,0.846）、86.67%（95% CI：0.684,0.956）,AUC分别为0.756（95% CI：0.651,0.860）、0.741（95% CI：0.633,0.848）、0.739（95% CI：0.631,0.846）、0.907（95% CI：0.842,0.972）。结论 ADC、K_trans、miR-221联合诊断前列腺癌效能较高,3者联合诊断前列腺癌可提供更加精确可靠的量化参数。     

mCTA侧支循环评分及血清microRNA-134、VEGF、bFGF水平预测AIS大脑中动脉闭塞患者预后的价值

目的 探究多时相计算机断层扫描血管成像（mCTA）侧支循环评分及血清microRNA-134（miR-134）、血管内皮细胞生长因子（VEGF）和碱性成纤维细胞生长因子（bFGF）水平预测急性缺血性脑卒中（AIS）大脑中动脉闭塞患者预后的价值。方法 选取2020年2月—2023年2月在江苏大学附属武进医院住院治疗的AIS大脑中动脉闭塞患者108例。检测患者治疗期间的mCTA侧支循环评分及血清miR-134、VEGF、bFGF水平,并进行随访。根据患者出院后3个月的改良Rankin量表评分,分为预后良好组（改良Rankin量表评分≤ 2分,47例）、预后不良组（改良Rankin量表评分> 2分,61例）,对可能影响患者预后的因素进行分析,并绘制ROC曲线分析其诊断价值。结果 预后不良组最终梗死体积大于预后良好组（P <0.05）,mCTA侧支循环评分低于预后良好组（P <0.05）;预后不良组miR-134相对表达量高于预后良好组（P <0.05）,VEGF、bFGF水平均低于预后良好组（P <0.05）。预后不良组年龄、低密度脂蛋白水平高于预后良好组（P <0.05）。多因素一般Logistic回归分析结果显示：mCTA侧支循环评分［O^R=0.804（95% CI：0.729,0.974）］、VEGF［O^R=0.618（95% CI：0.397,0.963）］、bFGF［O^R=0.608（95% CI：0.402,0.919）］为AIS大脑中动脉闭塞患者预后良好的保护性因素（P <0.05）;miR-134［O^R=1.941（95% CI：1.802,3.480）］、低密度脂蛋白［O^R=1.349（95% CI：1.051,1.730）］是AIS大脑中动脉闭塞患者预后不良的危险因素（P <0.05）。ROC曲线分析结果表明,mCTA侧支循环评分、miR-134、VEGF、bFGF预测AIS大脑中动脉闭塞患者预后不良的曲线下面积分别为0.843、0.946、0.937和0.892,敏感性分别为7.66%（95% CI：0.695,0.837）、9.36%（95% CI：0.900,0.972）、8.72%（95% CI：0.823,0.921）、7.23%（95% CI：0.661,0.785）,特异性分别为83.6%（95% CI：0.770,0.902）、82.0%（95% CI：0.770,0.870）、86.9%（95% CI：0.818,0.920）、93.4%（95% CI：0.896,0.972）。结论 预后不良患者最终梗死体积较大,mCTA侧支循环评分较低,血清miR-134、VEGF和bFGF水平较低。mCTA侧支循环评分、血清miR-134、VEGF、bFGF水平对AIS大脑中动脉闭塞患者预后不良有较好的预测价值,可作为预后评估的指标。     

MicroRNA-577/EIF5A2 axis suppressed the proliferation of DDP-resistant nasopharyngeal carcinoma cells by blocking TGF-β signaling pathway

Diaminodichoroplatinum (DDP) resistance of tumor cells is the culprit of nasopharyngeal carcinoma (NPC) treatment failure. MicroRNA-577 is lowly expressed in NPC tissues, but relevant mechanism is poorly studied. Therefore, this study investigated the role of microRNA-577 in NPC cells with DDP resistance and its mechanism. DDP-resistant NPC cells were established by treatment with DDP at increased concentrations (2, 4, 6, 8, or 10 μg/mL). MicroRNA-577 and EIF5A2 mRNA expressions were detected by qRT-PCR. Cell biological behaviors were assessed via cell function experiments. Expressions of epithelial mesenchymal transformation (EMT)-related proteins were quantified by western blot. The targeting relationship between eukaryotic translation initiation factor 5A2 (EIF5A2) and microRNA-577 was verified through dual-luciferase reporter assay. The tumor volume and weight were measured after subcutaneous tumorigenesis in mice. As observed from the results, microRNA-577 expression was reduced in NPC cells and DDP-resistant NPC cells. Up-regulated microRNA-577 suppressed the malignant behaviors and EMT of DDP-resistant NPC cells, and facilitated cell apoptosis. MicroRNA-577 targeted EIF5A2, and overexpressed EIF5A2 reversed the above effects of up-regulated microRNA-577 on DDP-resistant NPC cells. Besides, EIF5A2 positively regulated TGF-β signaling pathway, and TGF-β treatment offset the promoting effects of EIF5A2 silencing on apoptosis of DDP-resistant NPC cells. Up-regulated microRNA-577 suppressed the proliferation of DDP-resistant NPC cells, and down-regulated the levels of EIF5A2 and TGF-β as well as EMT in vivo. Collectively, microRNA-577/EIF5A2 axis hinders the EMT progression through the blockage of TGF-β signaling pathway, so as to inhibit the proliferation of DDP-resistant NPC.     

MicroRNA-34a-5p as a promising early circulating preclinical biomarker of doxorubicin-induced chronic cardiotoxicity

Cardiotoxicity is a serious adverse effect of an anticancer drug, doxorubicin (DOX), which can occur within a year or decades after completion of therapy. The present study was designed to address a knowledge gap concerning a lack of circulating biomarkers capable of predicting the risk of cardiotoxicity induced by DOX. Profiling of 2083 microRNAs (miRNAs) in mouse plasma revealed 81 differentially expressed miRNAs 1 week after 6, 9, 12, 18, or 24 mg/kg total cumulative DOX doses (early-onset model) or saline (SAL). Among these, the expression of seven miRNAs was altered prior to the onset of myocardial injury at 12 mg/kg and higher cumulative doses. The expression of only miR-34a-5p was significantly (false discovery rate [FDR] < 0.1) elevated at all total cumulative doses compared with concurrent SAL-treated controls and showed a statistically significant dose-related response. The trend in plasma miR-34a-5p expression levels during DOX exposures also correlated with a significant dose-related increase in cardiac expression of miR-34a-5p in these mice. Administration of a cardioprotective drug, dexrazoxane, to mice before DOX treatment, significantly mitigated miR-34a-5p expression in both plasma and heart in conjunction with attenuation of cardiac pathology. This association between plasma and heart may suggest miR-34a-5p as a potential early circulating marker of early-onset DOX cardiotoxicity. In addition, higher expression of miR-34a-5p (FDR < 0.1) in plasma and heart compared with SAL-treated controls 24 weeks after 24 mg/kg total cumulative DOX dose, when cardiac function was altered in our recently established delayed-onset cardiotoxicity model, indicated its potential as an early biomarker of delayed-onset cardiotoxicity.